Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald - Isle of Riems, Germany.
Nutritional Medicine Unit, Centre for Nutrition and Food Sciences, Technical University Munich, Gregor-Mendel-Straße 2, 85354 Freising, Germany.
J Gen Virol. 2013 Aug;94(Pt 8):1723-1733. doi: 10.1099/vir.0.052613-0. Epub 2013 May 8.
The underlying mechanisms allowing West Nile virus (WNV) to replicate in a large variety of different arthropod, bird and mammal species are largely unknown but are believed to rely on highly conserved proteins relevant for viral entry and replication. Consistent with this, the integrin αvβ3 has been proposed lately to function as the cellular receptor for WNV. More recently published data, however, are not in line with this concept. Integrins are highly conserved among diverse taxa and are expressed by almost every cell type at high numbers. Our study was designed to clarify the involvement of integrins in WNV infection of cells. A cell culture model, based on wild-type and specific integrin knockout cell lines lacking the integrin subunits αv, β1 or β3, was used to investigate the susceptibility to WNV, and to evaluate binding and replication efficiencies of four distinct strains (New York 1999, Uganda 1937, Sarafend and Dakar). Though all cell lines were permissive, clear differences in replication efficiencies were observed. Rescue of the β3-integrin subunit resulted in enhanced WNV yields of up to 90 %, regardless of the virus strain used. Similar results were obtained for β1-expressing and non-expressing cells. Binding, however, was not affected by the expression of the integrins in question, and integrin blocking antibodies failed to have any effect. We conclude that integrins are involved in WNV infection but not at the level of binding to target cells.
西尼罗河病毒（WNV）在多种不同的节肢动物、鸟类和哺乳动物物种中复制的潜在机制在很大程度上是未知的，但据信依赖于与病毒进入和复制相关的高度保守的蛋白质。与此一致，整合素 αvβ3 最近被提议作为 WNV 的细胞受体发挥作用。然而，最近发表的数据与这一概念不一致。整合素在不同的分类群中高度保守，几乎每种细胞类型都以高数量表达。我们的研究旨在阐明整合素在 WNV 感染细胞中的作用。我们使用基于野生型和特定整合素敲除细胞系的细胞培养模型，这些细胞系缺乏整合素亚基 αv、β1 或 β3，来研究对 WNV 的易感性，并评估四种不同毒株（纽约 1999 年、乌干达 1937 年、Sarafend 和达喀尔）的结合和复制效率。虽然所有细胞系都是允许的，但观察到复制效率有明显差异。β3 整合素亚基的拯救导致 WNV 产量增加了高达 90%，无论使用哪种病毒株。对于表达和不表达 β1 的细胞，也得到了类似的结果。然而，结合不受所涉及的整合素表达的影响，并且整合素阻断抗体没有任何效果。我们得出结论，整合素参与了 WNV 的感染，但不是在与靶细胞结合的水平上。
